Hu Wei, Liu Dongsheng, Li Renjie, Qian Hong, Qiu Wei, Ye Qingwang, Kong Fanyun
NanJing Drum Tower Hospital Group Suqian Hospital, The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, China.
Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical University, Xuzhou, China.
Front Genet. 2022 Jul 7;13:913743. doi: 10.3389/fgene.2022.913743. eCollection 2022.
As significant components of E3 ligases, the tripartite motif (TRIM) proteins participate in various biological processes and facilitate the development of several diseases. Nevertheless, the correlations of TIRMs with hepatitis B virus (HBV)-positive hepatoma carcinoma (HCC) are not well elaborated. The expression profile of TRIM genes in HBV-associated HCC and related clinical information were extracted from the Cancer Genome Atla (TCGA) database and the International Cancer Genome Consortium (ICGC) database. Dependent on the ConsensusPathDB and STRING databases, the gene ontology, Reactome pathways, and protein-protein interaction were assessed. Relied on TIMER 2.0 database, the relationship of the TRIMs with immune infiltration was investigated. Using multivariate analysis and Kaplan Meier analysis, the association between TRIM genes and the prognostic value was examined. A total of 17 TRIM genes, including TRIM16, TRIM17, and TRIM31 with fold change no less than 1.5, were discovered to upregulate in HBV-associated HCC in both TCGA and ICGC cohorts. Relied on gene enrichment analysis, the identified TRIMs were observed to not only be related to the interferon and cytokine signaling but also linked to the adaptive immune system. Particularly, the co-expression patterns of identified TRIMs with other E3 ligase genes and many innate immune genes that are associated with Toll-like receptor signaling, apoptosis, and SUMOylation. Besides, some of identified TRIM expressions were also linked to the infiltration levels of T cells and B cells. Additionally, several TRIM genes were associated with various clinical factors and relevant to the poor survival of HBV-associated HCC. Our findings could deepen our understanding of TRIMs and their correlations with HBV-associated HCC. Furthermore, some of these TRIMs may be utilized as new prognostic markers of HBV-related HCC prognosis, or act as potential molecular targets for the disease.
作为E3泛素连接酶的重要组成部分，三聚基序（TRIM）蛋白参与多种生物学过程，并促进多种疾病的发展。然而，TRIMs与乙型肝炎病毒（HBV）阳性肝癌（HCC）的相关性尚未得到充分阐述。从癌症基因组图谱（TCGA）数据库和国际癌症基因组联盟（ICGC）数据库中提取了TRIM基因在HBV相关HCC中的表达谱及相关临床信息。依托ConsensusPathDB和STRING数据库，对基因本体、Reactome通路和蛋白质-蛋白质相互作用进行了评估。借助TIMER 2.0数据库，研究了TRIMs与免疫浸润的关系。采用多变量分析和Kaplan Meier分析，检验了TRIM基因与预后价值之间的关联。在TCGA和ICGC队列中，共发现17个TRIM基因，包括TRIM16、TRIM17和TRIM31，其变化倍数不低于1.5，在HBV相关HCC中上调。通过基因富集分析发现，所鉴定的TRIMs不仅与干扰素和细胞因子信号传导有关，还与适应性免疫系统有关。特别是，所鉴定的TRIMs与其他E3泛素连接酶基因以及许多与Toll样受体信号传导、凋亡和SUMO化相关的先天免疫基因的共表达模式。此外，一些所鉴定的TRIM表达还与T细胞和B细胞的浸润水平有关。此外，几个TRIM基因与各种临床因素相关，并且与HBV相关HCC的不良生存有关。我们的研究结果可以加深我们对TRIMs及其与HBV相关HCC相关性的理解。此外，其中一些TRIMs可能被用作HBV相关HCC预后的新的预后标志物，或作为该疾病的潜在分子靶点。
